Analgin-darnitsa
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AANALGIN-DARNITSA (ANALGIN-DARNITSA)
Composition:
Active substance: metamizole sodium;
1 tablet contains 500 mg of sodium metamizole (analgin);
Excipients: potato starch, talc, calcium stearate.
Pharmaceutical form. Tablets.
Main physicochemical properties: white or slightly yellowish-white tablets, flat cylindrical in shape, with beveled edges and a score line.
Pharmacotherapeutic group. Analgesics and antipyretics. Pyrazolones. Sodium metamizole. ATC code N02BB02.
Pharmacological properties.
Pharmacodynamics.
A pyrazolone derivative, cyclooxygenase inhibitor. Reduces the formation of prostaglandins from arachidonic acid. Differs from other cyclooxygenase inhibitors by having a weak anti-inflammatory effect, while exhibiting pronounced analgesic, antipyretic, and spasmolytic actions. The spasmolytic effect is directed toward the smooth musculature of the urinary and biliary tracts.
Interferes with the conduction of extra- and proprioceptive pain impulses along the tracts of Goll and Burdah. Increases the excitation threshold of thalamic pain sensitivity centers and enhances heat dissipation.
Pharmacokinetics.
Rapidly absorbed from the gastrointestinal tract. Hydrolyzed in the intestinal wall to form an active metabolite. The unchanged compound is not present in the blood. The active metabolite is 50–60% bound to plasma proteins. Time to reach maximum plasma concentration is 1–2 hours. Elimination half-life (T1/2) is 2.5 hours. Excreted mainly by the kidneys.
Clinical characteristics.
Indications.
Pain syndrome of various origins: headache, toothache, neuralgia, radiculitis, muscle and joint pain, menstrual pain. As an adjunctive agent to reduce pain following surgical and diagnostic procedures. Hyperthermic syndrome in infectious-inflammatory diseases.
Contraindications.
Hypersensitivity to components of the drug, pyrazolone derivatives.
Changes in peripheral blood composition: agranulocytosis, leukopenia.
Blood disorders: anemia of any etiology, cytostatic or infectious neutropenia.
Severe impairment of liver and kidney function (porphyrin metabolism).
Congenital deficiency of glucose-6-phosphate dehydrogenase.
Bronchial asthma.
Suspicion of acute surgical pathology.
Interaction with other medicinal products and other types of interactions.
Ethanol – sedative effect of ethanol is enhanced.
Chlorpromazine or other phenothiazine derivatives – concomitant use may lead to development of pronounced hypothermia.
X-ray contrast agents, colloidal plasma substitutes, and penicillin – should not be used during treatment with sodium metamizole.
Cyclosporine – concomitant use reduces cyclosporine blood concentration.
Oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids, phenytoin, ibuprofen, and indometacin – sodium metamizole increases the activity of these drugs by displacing them from protein binding sites in blood.
Phenylbutazone, glutethimide, barbiturates, and other inducers of hepatic microsomal enzymes – concomitant use reduces the efficacy of sodium metamizole.
Non-narcotic analgesics, tricyclic antidepressants, hormonal contraceptives, and allopurinol – concomitant use with sodium metamizole may increase its toxicity.
Other non-steroidal anti-inflammatory drugs (NSAIDs) – their analgesic and antipyretic effects are potentiated, and the risk of additive adverse effects is increased.
Sedatives and tranquilizers (diazepam, trioxazine, valocordin) – enhance the analgesic effect of sodium metamizole.
Sarkolysin (melphalan), mercaptopurine, thiouracil derivatives (thiamazole), and drugs that suppress bone marrow activity, including gold-containing drugs – increased risk of hematotoxicity, including development of leukopenia.
Codeine, histamine H2-blockers, and propranolol – enhance the effect of sodium metamizole.
Caution is required when using the drug concomitantly with sulfonylurea hypoglycemic agents (hypoglycemic effect is potentiated) and diuretics (furosemide).
Myelotoxic medicinal products lead to increased hematotoxicity.
Metotrexate – high doses of metamizole may increase plasma concentration of methotrexate and enhance its toxic effects (on the gastrointestinal tract and hematopoietic system).
Special precautions for use.
Before starting treatment with the medicinal product, consult a physician.
Do not exceed the recommended doses of the medicinal product.
Severe skin reactions
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced eosinophilia with systemic symptoms (DRESS syndrome), which may be life-threatening or fatal, have been reported during treatment with metamizole.
Patients should be informed about the signs and symptoms of skin reactions and closely monitored.
If signs or symptoms indicating these reactions occur, treatment with metamizole should be discontinued immediately and must never be restarted (see section "Contraindications").
Do not use the medicinal product to relieve acute abdominal pain (before determining the cause). Since sodium metamizole has anti-inflammatory and analgesic properties, it may mask signs of infection, symptoms of non-infectious diseases, and complications associated with pain, which could complicate their diagnosis.
Alcohol consumption should be avoided during treatment with this medicinal product.
The medicinal product should be used with caution in patients:
- of advanced age – may lead to an increased frequency of adverse reactions, especially those affecting the gastrointestinal system;
- with existing allergic diseases (including hay fever) or a previous history of such conditions – risk of allergic reactions is increased;
- with impaired kidney function or a history of kidney disease (pyelonephritis, glomerulonephritis);
- with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease;
- with marked arterial hypotension or cardiovascular insufficiency;
- with a history of chronic alcohol use;
- when used concomitantly with cytostatic medicinal products (only under physician supervision).
When used in children, continuous medical supervision is required.
When using the medicinal product, monitoring of peripheral blood composition (leukocyte formula) is not required.
Regular long-term use of the medicinal product is not recommended due to the myelotoxicity of sodium metamizole.
When the medicinal product is used long-term (more than 7 days), monitoring of peripheral blood composition (due to myelotoxicity of metamizole), as well as kidney and liver function, is necessary.
Drug-induced liver injury
Cases of drug-induced liver injury, mainly of hepatocellular type, have been observed in patients treated with metamizole, occurring several days or months after initiation of treatment. Signs and symptoms include elevated serum liver enzymes, with or without jaundice, often accompanied by hypersensitivity reactions to other drugs (e.g., skin rash, blood dyscrasias, fever, and eosinophilia), or associated with signs of autoimmune hepatitis. In most patients, the condition resolved after discontinuation of metamizole therapy. However, isolated cases of progression to acute liver failure requiring liver transplantation have been reported.
The mechanism of liver injury caused by metamizole is not fully understood, although available data suggest an immune-allergic mechanism.
Patients should be informed about the need to consult a physician if symptoms indicating liver injury occur. In such cases, metamizole should be discontinued and liver function assessed.
If symptoms such as nausea and vomiting, fever, fatigue, loss of appetite, darkening of urine, light-colored stools, jaundice of the skin or sclera, pruritus, skin rash, or upper abdominal pain occur, metamizole should be discontinued immediately and medical advice sought. Metamizole must not be re-administered to patients who experienced liver injury during previous treatment with metamizole unless other causes of liver injury have been ruled out.
Patients should be warned before starting treatment that if unexplained chills, fever, sore throat, difficulty swallowing, bleeding gums, pallor of the skin, asthenia, or development of vaginitis or proctitis occur, the medicinal product must be discontinued immediately. The use of the medicinal product should also be stopped if skin or mucosal rashes appear. In case of these symptoms, immediate medical consultation is required.
During treatment with the medicinal product, red discoloration of urine may occur due to excretion of sodium metamizole metabolites.
Do not use the medicinal product beyond the established duration without consulting a physician.
If symptoms of illness do not begin to subside, or conversely, if the patient's condition worsens, or if adverse effects occur, discontinue use of the medicinal product and consult a physician regarding further treatment.
Use during pregnancy or breastfeeding.
The medicinal product is contraindicated during pregnancy. Breastfeeding should be discontinued during treatment.
Ability to affect reaction speed when driving or operating machinery.
Does not affect.
Method of Administration and Dosage
Administer to adults and children aged 14 years and older orally, 250–500 mg (½–1 tablet) 1–2 times daily. Tablets should be taken after meals, without chewing or crushing, and swallowed with sufficient amount of water.
Maximum daily dose − 1 g.
Children aged 12 to 14 years − 250 mg 1–2 times daily.
Metamizole is intended for symptomatic short-term use only. Treatment duration should not exceed 3 days.
If symptoms do not resolve within 3 days, consult a physician regarding further use of the medicinal product.
Children
The medicinal product must not be administered to children under 12 years of age.
Overdose.
Symptoms: hypothermia, palpitations, marked decrease in arterial blood pressure, tachycardia, dysphagia, dyspnea, tinnitus, nausea, vomiting, gastralgia/gastritis, weakness, drowsiness, delirium, impaired consciousness, convulsive syndrome; acute agranulocytosis, hemorrhagic syndrome, oliguria, anuria, acute renal and hepatic failure, respiratory muscle paralysis may develop.
Treatment: discontinue the drug, induce vomiting, gastric lavage, administer saline laxatives and enterosorbents, forced diuresis, symptomatic therapy aimed at supporting vital functions. In severe cases, hemodialysis, hemoperfusion, or peritoneal dialysis may be considered.
In case of first signs of overdose, seek immediate medical attention!
Side effects.
Hepatic and biliary disorders: hepatitis, drug-induced liver injury, including acute hepatitis, jaundice, increased levels of liver enzymes (see section "Special precautions for use").
Renal and urinary disorders: oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.
Cardiovascular disorders: decreased blood pressure, tachycardia.
Blood and lymphatic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia.
Immune system disorders: hypersensitivity reactions, including skin and mucosal rashes, skin hyperemia, pruritus, urticaria, conjunctivitis, Quincke's edema; bronchospastic syndrome, anaphylactoid reactions, anaphylactic shock.
Skin and subcutaneous tissue disorders: rarely – Stevens-Johnson syndrome, Lyell's syndrome; frequency not known – drug reaction with eosinophilia and systemic symptoms (DRESS).
General disorders and administration site conditions: infiltrates at the injection site (with intramuscular administration), hyperemia, swelling, local skin rashes, and pruritus at the injection site.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after drug registration is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.
Shelf life. 5 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging.
10 tablets in a blister pack; 1 blister pack in a carton; 10 tablets in blister packs.
Prescription status. Over-the-counter.
Manufacturer. JSC "Pharmaceutical Company "Darnytsia".
Manufacturer's address and location of its business activity.
13 Borispilska Street, Kyiv, 02093, Ukraine.